tbuckley/cabot-search huggingface dataset:
<i>RBM10</i> Loss Promotes <i>EGFR</i>-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition
Authors: Yufang Bao, Sirui Zhang, Xiaoyu Zhang, Yunjian Pan, Yueren Yan, Ning Wang, Yunpeng Ren, Ji Zuo, Wei-Xing Zong, Zefeng Wang, Yongbo Wang
Journal: Cancer Research (2023)

Abstract In lung adenocarcinoma (LUAD), loss-of-function mutations in the splicing factor RBM10 frequently co-occur with oncogenic EGFR mutations. A detailed understanding of the functional consequences and therapeutic impact of RBM10 loss in EGFR-mutant LUAD could help identify more effective treatment strategies. Here, analysis of LUAD data sets indicated that RBM10 mutations are mutually exclusive with mutations in the tumor suppressor gene TP53. In an EGFR-driven LUAD mouse model, lung-specific ablation of either Rbm10 or Trp53 similarly promoted tumor development, leading to overlapping gene expression changes enriched in cancer-related pathways. RBM10 loss induced key RNA splicing changes concordant in mice and LUAD patients. Importantly, RBM10 deficiency conferred high sensitivity to spliceosome inhibition in EGFR-mutated LUAD cells. Combined treatment with spliceosome inhibitor improved the therapeutic efficacy of EGFR tyrosine kinase inhibitor osimertinib and overcame drug resistance, especially in RBM10-deficient LUAD. Together, this study establishes RBM10 as a tumor suppressor akin to p53 and provides a therapeutic strategy of targeting the splicing machinery in EGFR-driven LUAD. Significance: Loss of the splicing factor RBM10 is mutually exclusive with p53 mutations, promotes tumorigenesis, and enhances the efficacy of spliceosome inhibition in EGFR-driven lung cancer.
Discovery of Transacting Long Noncoding RNAs That Regulate Smooth Muscle Cell Phenotype
Authors: Huitong Shi, Trieu Nguyen, Quanyi Zhao, Paul Cheng, Disha Sharma, Hyun-Jung Kim, Juyong Brian Kim, Robert Wirka, Chad S. Weldy, João P. Monteiro, Thomas Quertermous
Journal: Circulation Research (2023)

Smooth muscle cells (SMC), the major cell type in atherosclerotic plaques, are vital in coronary artery diseases (CADs). SMC phenotypic transition, which leads to the formation of various cell types in atherosclerotic plaques, is regulated by a network of genetic and epigenetic mechanisms and governs the risk of disease. The involvement of long noncoding RNAs (lncRNAs) has been increasingly identified in cardiovascular disease. However, SMC lncRNAs have not been comprehensively characterized, and their regulatory role in SMC state transition remains unknown.
Cefepime/Enmetazobactam vs Piperacillin/Tazobactam and Complicated Urinary Tract Infection or Acute Pyelonephritis
Authors: Chi-Kuei Hsu, Wen-Wen Tsai, Chih-Cheng Lai
Journal: JAMA (2023)

To the Editor A recent trial1 comparing the effect of cefepime/enmetazobactam vs piperacillin/tazobactam on complicated urinary tract infection or acute pyelonephritis found that patients receiving cefepime/enmetazobactam had a better primary outcome. We have some concerns about this study.
Gender, Racial, and Ethnic Inequities in Receipt of Multiple National Institutes of Health Research Project Grants
Authors: Mytien Nguyen, Sarwat I. Chaudhry, Mayur M. Desai, Kafui Dzirasa, Jose E. Cavazos, Dowin Boatright
Journal: JAMA Network Open (2023)

Importance Diversity in the biomedical research workforce is essential for addressing complex health problems. Female investigators and investigators from underrepresented ethnic and racial groups generate novel, impactful, and innovative research, yet they are significantly underrepresented among National Institutes of Health (NIH) investigators. Objective To examine the gender, ethnic, and racial distribution of super NIH investigators who received 3 or more concurrent NIH grants. Design, Setting, and Participants This cross-sectional study included a national cohort of NIH-funded principal investigators (PIs) from the NIH Information for Management, Planning, Analysis, and Coordination (IMPAC II) database from 1991 to 2020. Exposures Self-identified gender, race and ethnicity, annual number of NIH grant receipt, career stage, and highest degree. Main Outcomes and Measures Distribution of investigators receiving 3 or more research project grants, referred to as super principal investigators (SPIs), by gender, race, and ethnicity. Results Among 33 896 investigators in fiscal year 2020, 7478 (22.01%) identified as Asian, 623 (1.8%) as Black, 1624 (4.8%) as Hispanic, and 22 107 (65.2%) as White; 21 936 (61.7%) identified as men; and 8695 (35.3%) were early-stage investigators. Between 1991 and 2020, the proportion of SPIs increased 3-fold from 704 (3.7%) to 3942 (11.3%). However, SPI status was unequal across gender, ethnic, and racial groups. Women and Black PIs were significantly underrepresented among SPIs, even after adjusting for career stage and degree, and were 34% and 40% less likely than their male and White colleagues, respectively, to be an SPI. Black women PIs were the least likely to be represented among SPIs and were 71% less likely to attain SPI status than White men PIs (adjusted odds ratio, 0.29; 95% CI, 0.21-0.41). Conclusions and Relevance In this cross-sectional study of a national cohort of NIH-funded investigators, the gender, ethnic, and racial gaps in receipt of multiple research project grants among NIH investigators was clearly apparent and warrants further investigation and interventions.
Is There a Role for Renal Denervation in the Treatment of Hypertension?
Authors: Clyde W. Yancy, Gregg C. Fonarow, Patrick T. O’Gara
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Phase II Study of Palbociclib (PD-0332991) in<i>CCND1</i>,<i>2</i>, or<i>3</i>Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B
Authors: Amy S. Clark, Fangxin Hong, Richard S. Finn, Angela M. DeMichele, Edith P. Mitchell, James Zwiebel, Fernanda I. Arnaldez, Robert J. Gray, Victoria Wang, Lisa M. McShane, Larry V. Rubinstein, David Patton, P. Mickey Williams, Stanley R. Hamilton, Mehmet S. Copur, Samer S. Kasbari, Ravneet Thind, Barbara A. Conley, Carlos L. Arteaga, Peter J. O'Dwyer, Lyndsay N. Harris, Alice P. Chen, Keith T. Flaherty
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3. Patients and Methods: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of a 28-day cycle. Tumor response was assessed every two cycles. Results: Forty patients were assigned to subprotocol Z1B; 4 patients had outside assays identifying the CCND1, 2, or 3 amplification and were not confirmed centrally; 3 were ineligible and 2 were not treated (1 untreated patient was also ineligible), leaving 32 evaluable patients for this analysis. There were no partial responses; 12 patients (37.5%) had stable disease as best response. There were seven deaths on study, all during cycle 1 and attributable to disease progression. Median progression-free survival was 1.8 months. The most common toxicities were leukopenia (n = 21, 55%) and neutropenia (n = 19, 50%); neutropenia was the most common grade 3/4 event (n = 12, 32%). Conclusions: Palbociclib was not effective at treating nonbreast solid tumors with a CCND1, 2, or 3 amplification in this cohort. These data do not support further investigation of single-agent palbociclib in tumors with CCND1, 2, or 3 amplification.
The long-range interaction between two GNAS imprinting control regions delineates pseudohypoparathyroidism type 1B pathogenesis
Authors: Yorihiro Iwasaki, Cagri Aksu, Monica Reyes, Birol Ay, Qing He, Murat Bastepe
Journal: Journal of Clinical Investigation (2023)

Genetic defects of GNAS, the imprinted gene encoding the stimulatory G protein α-subunit, are responsible for multiple diseases. Abnormal GNAS imprinting causes pseudohypoparathyroidism type 1B (PHP1B), a prototype of mammalian end-organ hormone resistance. Hypomethylation at the maternally methylated GNAS A/B region is the only shared defect in patients with PHP1B. In autosomal dominant (AD) PHP1B kindreds, A/B hypomethylation is associated with maternal microdeletions at either the GNAS NESP55 differentially methylated region or the STX16 gene located approximately 170 kb upstream. Functional evidence is meager regarding the causality of these microdeletions. Moreover, the mechanisms linking A/B methylation and the putative imprinting control regions (ICRs) NESP-ICR and STX16-ICR remain unknown. Here, we generated a human embryonic stem cell model of AD-PHP1B by introducing ICR deletions using CRISPR/Cas9. With this model, we showed that the NESP-ICR is required for methylation and transcriptional silencing of A/B on the maternal allele. We also found that the SXT16-ICR is a long-range enhancer of NESP55 transcription, which originates from the maternal NESP-ICR. Furthermore, we demonstrated that the STX16-ICR is an embryonic stage–specific enhancer enabled by the direct binding of pluripotency factors. Our findings uncover an essential GNAS imprinting control mechanism and advance the molecular understanding of PHP1B pathogenesis.
Decitabine priming increases anti–PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models
Authors: Xiang Li, Yaru Li, Liang Dong, Yixin Chang, Xingying Zhang, Chunmeng Wang, Meixia Chen, Xiaochen Bo, Hebing Chen, Weidong Han, Jing Nie
Journal: Journal of Clinical Investigation (2023)

CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability to maintain a capacity for durable proliferation of progenitor Tex is important, but the mechanism remains unclear. Here, we showed CD8+ progenitor Tex pretreated with decitabine, a low-dose DNA demethylating agent, had enhanced proliferation and effector function against tumors after anti–PD-1 treatment in vitro. Treatment with decitabine plus anti–PD-1 promoted the activation and expansion of tumor-infiltrated CD8+ progenitor Tex and efficiently suppressed tumor growth in multiple tumor models. Transcriptional and epigenetic profiling of tumor-infiltrated T cells demonstrated that the combination of decitabine plus anti–PD-1 markedly elevated the clonal expansion and cytolytic activity of progenitor Tex compared with anti–PD-1 monotherapy and restrained CD8+ T cell terminal differentiation. Strikingly, decitabine plus anti–PD-1 sustained the expression and activity of the AP-1 transcription factor JunD, which was reduced following PD-1 blockade therapy. Downregulation of JunD repressed T cell proliferation, and activation of JNK/AP-1 signaling in CD8+ T cells enhanced the antitumor capacity of PD-1 inhibitors. Together, epigenetic agents remodel CD8+ progenitor Tex populations and improve responsiveness to anti–PD-1 therapy.
Incorrect Data in Table
Authors: Ralph Snyderman
Journal: JAMA (2023)

Margaret A. McConnell, PhD; Slawa Rokicki, PhD; Samuel Ayers, BA; Farah Allouch, MPH; Nicolas Perreault, MS; Rebecca A. Gourevitch, MS, PhD; Michelle W. Martin, PhD; R. Annetta Zhou, PhD; Chloe Zera, MPH, MD; Michele R. Hacker, ScD; Alyna Chien, MS, MD; Mary Ann Bates, MPP; Katherine Baicker, PhD
Last Name Misspelled
Journal: JAMA (2023)

Magnus Ekström, MD, PhD; Diana Ferreira, MD, PhD; Sungwon Chang, PhD; Sandra Louw, BSc; Miriam J. Johnson, MD, MBChB; Danny J. Eckert, PhD; Belinda Fazekas, GDip; Katherine J. Clark, PhD; Meera R. Agar, PhD; David C. Currow, MPH, PhD; Australian National Palliative Care Clinical Studies Collaborative; Christine McDonald Prof; John Miners Prof; Carl Kirkpatrick Prof; Andrew Somogyi Prof; Linda Denehy Prof; Nikki McCaffrey Dr; Lawrence Lam Prof; Aine Greene Ms; Brian Le Dr; Katherine Clark Prof; Kwun Fong Prof; Meera Agar Prof; Rohit Joshi Dr; Sharon Kilbreath Prof; Diana Ferreira Dr; Angela Clow Prof; Nina Smith Dr; Richella Ryan Dr; Sara Booth Dr; Peter Martin Prof; Suharsha Kanathigoda Dr; Caitlin Sheehan Dr; Jessica Lee Dr; Peter Allcroft Dr; Erica Cameron-Taylor Dr; Philip Good Dr; Louise Welch Dr; Richard Chye Prof; Jennifer Phillip Prof; John Wheatley Prof; Anu krishnan Dr; Michael Epton Dr; Rajesh Aggarwal Dr; Philip McCloud Mr; Jessie Chan Ms; Douglas Bellamy Mr; Frances Bellemore Ms; Priyanka Bhatarai Ms; Helen Biggins Ms; Mary-Rose Birch Ms; Lesley Burke Ms; Tracey Burns Ms; Naomi Byfieldt Ms; Diana Charlesworth Ms; Gillian Collins Ms; Helen Cooper Ms; Urska Cosic Ms; Deborah Courtney Ms; Georgie Cupples Ms; Anna Dowd Ms; Ruth Dunleavey Ms; Terence Edgar Mr; Amanda Fischer Ms; Lisa Fuhrmeister Ms; Jan Gesling Ms; Rosetta Hart Ms; Kim Hopkinson Ms; Michelle Kaczurowski Ms; Sally Kidd Ms; Ngaire Kingi Ms; Vera Margitanovic Ms; Gillian McCarthy Ms; Robin O'Reilly Ms; Mary Perry Ms; Bronwyn Raymond Ms; Di Saward Ms; Aaron Shanon-Honson Mr; Karyn Sullivan Ms; Michelle Tonkin Ms; Zac Vandersman Mr; Penny West Ms; Julie Wilcock Ms; Malina Storer Dr; Sarah Nestor Dr; Safrina Thristiawati Ms; Manraaj Sidhu Mr
Association of Evaluation and Management Payment Policy Changes With Medicare Payment to Physicians by Specialty
Authors: Hannah T. Neprash, Ezra Golberstein, Ishani Ganguli, Michael E. Chernew
Journal: JAMA (2023)

US primary care physicians (PCPs) have lower mean incomes than specialists, likely contributing to workforce shortages. In 2021, the Centers for Medicare & Medicaid Services increased payment for evaluation and management (E/M) services and relaxed documentation requirements. These changes may have reduced the gap between primary care and specialist payment.To simulate the effect of the E/M payment policy change on total Medicare physician payments while holding volume constant and to compare these simulated changes with observed changes in total Medicare payments and E/M coding intensity, before (July-December 2020) and after (July-December 2021) the E/M payment policy change.Retrospective observational study of US office-based physicians who were in specialties with 5000 or more physicians billing Medicare and who had 50 or more fee-for-service Medicare visits before and after the E/M payment policy change.E/M payment policy changes.Outcomes included physician-level simulated volume-constant payment change, total observed Medicare payment change, and share of high-intensity (ie, level 4 or 5) E/M visits before and after the E/M payment policy change. For each specialty, the median change in each outcome was reported. The payment gap between primary care and specialty physicians was calculated as the difference between total Medicare payments to the median primary care and median specialty physician.The study population included 180 624 physicians. Repricing 2020 services yielded a simulated volume-constant payment change ranging from a 3.3% (-$4557.0) decrease for the median radiologist to an 11.0% ($3683.1) increase for the median family practice physician. After the E/M payment change, the median high-intensity share of E/M visits increased for physicians of nearly all specialties, ranging from a -4.4 percentage point increase (dermatology) to a 17.8 percentage point increase (psychiatry). The median change in total Medicare payments by specialty ranged from -4.2% (-$1782.9) for general surgery to 12.1% ($3746.9) for family practice. From July-December 2020 to July-December 2021, the payment gap between the median primary care physician and the median specialist shrank by $825.1, from $40 259.8 to $39 434.7 (primary care, $41 193.3 in July-December 2020 and $45 962.4 in July-December 2021; specialist, $81 453.1 in July-December 2020 and $85 397.1 in July-December 2021)-a relative decrease of 2.0%.Among US office-based physicians receiving Medicare payments in 2020 and 2021, E/M payment policy changes were associated with changes in Medicare payment by specialty, although the payment gap between primary care physicians and specialists decreased only modestly. The findings may have been influenced by the COVID-19 pandemic, and further research in subsequent years is needed.
Hydroxychloroquine Dose and Risk of Systemic Lupus Erythematosus Flares
Authors: Fernando Caravaca-Fontán, Federico Yandian, Fernando C. Fervenza
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Locoregional Treatment of Glioblastoma With Targeted α Therapy
Authors: Leszek Królicki, Jolanta Kunikowska, Frank Bruchertseifer, Radosław Kuliński, Dariusz Pawlak, Henryk Koziara, Rafał Rola, Alfred Morgenstern, Adrian Merlo
Journal: Clinical Nuclear Medicine (2023)

Glioblastoma (GB) is the most malignant primary brain tumor. Therefore, introduction of new treatment options is critically important. The aim of this study was to assess local treatment with α emitters [ 213 Bi]Bi-DOTA-substance P (SP) and [ 225 Ac]Ac-DOTA-SP.Treatment was performed as salvage therapy in patients with recurrent primary and secondary GB. [ 213 Bi]Bi-DOTA-SP with injected activity 1.85 GBq per cycle was used in 20 primary (48.2 ± 11.8 years old) and in 9 secondary (38.8 ± 10.8 years old) GB patients and [ 225 Ac]Ac-DOTA-SP in 15 primary (45.1 ± 9.9 years old) and in 6 secondary (37.8 ± 6.4 years old) GB patients with a dose escalation scheme (10, 20, and 30 MBq).Local treatment with [ 213 Bi]Bi-DOTA-SP and [ 225 Ac]Ac-DOTA-SP was well tolerated with only few adverse effects. There was no statistically significant difference between [ 213 Bi]Bi-DOTA-SP and [ 225 Ac]Ac-DOTA-SP groups in survival parameters. For primary GB, survival parameters of patients treated with [ 213 Bi]Bi-DOTA-SP and [ 225 Ac]Ac-DOTA-SP were as follows(in months): progression-free survival time, 2.7 versus 2.4; OS-d (overall survival from time of diagnosis to death from any cause), 23.6 versus 21.0; OS-t (overall survival from the start of treatment to death from any cause), 7.5 versus 5.0; and OS-r (overall survival from recurrence in primary tumors to death from any cause), 10.9 versus 12.0. Survival parameters of secondary GB patients treated with [ 213 Bi]Bi-DOTA-SP and [ 225 Ac]Ac-DOTA-SP were as follows (in months): progression-free survival time, 5.8 versus 2.4; OS-d, 52.3 versus 65.0; OS-t, 16.4 versus 16.0; and OS-c (overall survival from conversion into secondary GB multiforme to death from any cause), 18.4 versus 36.0.The similarity results of 213 Bi or 225 Ac may suggest that the local treatment of brain tumors can be greatly simplified. The experience to date shows that local radioisotope treatment of brain tumors requires further dosimetry studies, taking into account the complexity of biological processes.
Sustained Release of BMSC‐EVs from 3D Printing Gel/HA/nHAP Scaffolds for Promoting Bone Regeneration in Diabetic Rats
Authors: Tingting Yang, Yunsheng Dong, Jinpeng Wan, Xiangsheng Liu, Yufei Liu, Jiaxing Huang, Jie Zhou, Hui Xiao, Lizong Tang, Yanying Wang, Shufang Wang, Hong Cai
Journal: Advanced Healthcare Materials (2023)

Extracellular vesicles (EVs) play an important role in intercellular communication, and the function of EVs mainly depends on the state of source cells. To determine the effect of diabetic microenvironment on EVs secreted by bone marrow mesenchymal stem cells (BMSCs), this work explores the effect of normal glucose (5.5 mm) cultured BMSCs derived EVs (NG-EVs) and high glucose (30 mm) cultured BMSCs derived EVs (HG-EVs) in regulating the migration, proliferation and osteoblastic differentiation of BMSCs in vitro. In order to improve the bioavailability of EVs, this work constructs a sustained release system of polydopamine (PDA) functionalized 3D printing gelatin/hyaluronic acid/nano-hydroxyapatite (Gel/HA/nHAP) scaffolds (S/PDA) and verifies its function in the calvarial defect model of diabetic rats. This work confirms that both NG-EVs and HG-EVs can promote proliferation and migration, inhibit apoptosis and promote osteogenic differentiation, but the function of HG-EVs is weaker than that of NG-EVs. Therefore, EVs secreted by autologous cells of diabetic patients are not suitable for self-repair. This work hopes that the 3D printing scaffold designed for sustained-release EVs will provide a new strategy for acellular tissue engineering bone repair in diabetic patients.
Cryptic lncRNA-encoded ORFs: A hidden source of regulatory proteins
Authors: Anindya Dutta, Hui Li, Roger Abounader
Journal: Journal of Clinical Investigation (2023)

A majority of the human genome is transcribed into noncoding RNAs, of which long noncoding RNAs (lncRNAs) form a large and heterogeneous fraction. While lncRNAs are mostly noncoding, recent evidence suggests that cryptic translation within some lncRNAs may produce proteins with important regulatory functions. In this issue of the JCI, Zheng, Wei, and colleagues used an integrative functional genomic strategy to systematically identify cryptic lncRNA-encoded ORFs that play a role in estrogen receptor–positive (ER+) breast cancer (BC). They identified 758 cryptic lncRNA-encoded ORFs undergoing active translation, of which 28 had potential functional and clinical relevance in ER+ BC. The LINC00992-encoded polypeptide GT3-INCP was upregulated in ER+ BC and drove tumor growth. GT3-INCP was regulated by estrogen and the ER and acted via the transcription factor GATA3 to regulate BC susceptibility and risk genes. These findings discern a largely unexplored class of molecules and have implications for many pathologies, including cancer.